186,408 research outputs found

    Phenotypic Modulation and Neuroprotective Effects of Olfactory Ensheathing Cells : a Promising Tool for Cell Therapy

    No full text
    Olfactory Ensheathing Cells (OECs), exhibiting phenotypic characteristics of both astrocytes and Schwann Cells, show peculiar plasticity. In vitro, OECs promote axonal growth, while in vivo they promote remyelination of damaged axons. We decided to further investigate OEC potential for regeneration and functional recovery of the damaged Central Nervous System (CNS). To study OEC antigen modulation, OECs prepared from postnatal mouse olfactory bulbs were grown in different culture conditions: standard or serum-free media with/without Growth Factors (GFs) and analyzed for different neural specific markers. OEC functional characterizations were also achieved. Resistance of OECs to the neurotoxin 6-hydroxydopamine (6-OHDA) was analyzed by evaluating apoptosis and death. OEC neuroprotective properties were investigated by in vitro co-cultures or by addition of OEC conditioned medium to the neuroblastoma SH-SY5Y cells exposed to 6-OHDA. We observed: 1) modification of OEC morphology, reduced cell survival and marker expression in serum-free medium; 2) GF addition to serum-free medium condition influenced positively survival and restored basal marker expression; 3) no OEC apoptosis after a prolonged exposition to 6-OHDA; 4) a clear OEC neuroprotective tendency, albeit non statistically significant, on 6-OHDA treated SH-SY5Y cells. These peculiar properties of OECs might render them potential clinical agents able to support injured CNS

    Parasympathetic tone and its adaptation to aerobic training (Fitwalking®) in HIV patients on anti-retroviral therapy

    No full text
    Recent evidences showed that in HIV patients Highly Active Antiretroviral Therapy (HAART) and HIV per se may affect parasympathetic tone; this may increase the cardiovascular risk and contribute to HIV associated lipodystrophy. Such impairment may be reversed by a regular physical activity, which is known to increase vagal tone. PURPOSE: To evaluate vagal tone and its change after 3 months of aerobic training in HIV patients on HAART. METHODS: 12 non-hypertensive and non-smoker patients (F/M 2/10; 47±5 yrs; 71±14 kg) with HIV infection (H) on HAART were enrolled. A group of 12 control (C) subjects (F/M 3/9; 48±12 yrs; 76±13 kg), matched for gender, age and anthropometric features, was enrolled for baseline comparisons. Heart rate variability (HRV) indexes of parasympathetic tone in time (RMSSD, pNN50) and frequency (High Frequency [HF] in absolute and normalized units [nu]) domains, and a HRV index of sympathovagal balance (LF/HF ratio) were calculated in basal condition in H and C subjects, both in supine and standing position for 5 min each, by a HR monitor. The H group was then trained by walking at 60-70% of maximal HR 3 times/week for 12 weeks, and the HRV measures were repeated thereafter. A 6-min walking test (6MWT) was executed before and after the training. RESULTS: In basal condition, despite similar values in supine position between H and C subjects, HIV patients showed a lower parasympathetic tone during standing, which was significant in the linear indexes (RMSSD: H 16.7±5.1 vs C 25.3±10.5 ms [p<0.05]; pNN50: H 1.4±1.3 vs C 5.4±5.3% [p<0.05]; HF: H 180±207 vs C 196±139 ms2; HFnu: H 21.6±23.5 vs C 27.0±16.2), and a higher sympathetic activation (LF/HF: H 9.2±7.0 vs C 4.1±2.7 [p=0.04]) compared to C subjects. Fitwalking® training significantly improved the distance covered by 6MWT (from 667±50 to 802±160 m, p=0.01) and the physical work done (from 451±96 to 538±132 J, p=0.01). However, standing values of HRV indexes did not significantly change after training in H patients (RMSSD 15.2±6.6 ms, pNN50 1.1±1.7%, HF 100±93 ms2, HFnu 11.5±6.7, LF/HF 9.7±7.5; p=ns vs pre-training for all comparisons). CONCLUSIONS: 12-weeks aerobic training improved cardiovascular fitness in HIV patients, but did not affect the heart parasympathetic control, which remained reduced compared to healthy subjects

    Detection of DNA of lymphotropic herpesviruses in plasma of human immunodeficiency virus-infected patients: Frequency and clinical significance

    No full text
    The frequency and clinical significance of detection of DNA of cytomegalovirus (CMV), Epstein-Barr virus (EBV), human herpesvirus 6 (HHV-6), HHV-7, and HHV-8 in plasma were investigated by PCR. The plasma was obtained from 120 selected human immunodeficiency virus (HIV)-infected patients, of whom 75 had AIDS-related manifestations, 32 had primary HIV infection (PHI), and 13 had asymptomatic infections. Nested PCR analysis revealed that none of the lymphotropic herpesviruses tested were found in patients with PHI, in asymptomatic HIV-positive individuals, or in HIV-negative controls. By contrast, DNA of one or more of the viruses was found in 42 (56%) of 75 patients with AIDS-related manifestations, including CMV disease (CMV-D) or AIDS-related tumors. The presence of CMV DNA in plasma was significantly associated with CMV-D (P < 0.001). By contrast, EBV detection was not significantly associated with AIDS-related lymphomas (P = 0.31). Interestingly, the presence of HHV-8 DNA in plasma was significantly associated with Kaposi's sarcoma (KS) disease (P < 0.001) and with the clinical status of KS patients (P < 0.001). CMV (primarily), EBV, and HHV-8 were the viruses most commonly reactivated in the context of severe immunosuppression (P < 0.05). In contrast, HHV-6 and HHV-7 infections were infrequent at any stage of disease. In conclusion, plasma PCR was confirmed to be useful in the diagnosis of CMV-D but not in that of tumors or other conditions possibly associated with EBV, HHV-6, and HHV-7. Our findings support the hypothesis of a direct involvement of HHV-8 replication in KS pathogenesis, thus emphasizing the usefulness of sensitive and specific diagnostic tests to monitor HHV-8 infectio

    Benefits of brisk walking as moderate on soluble and cell markers of inflammation in HIV-infected persons receiving anti-HIV drugs : a pilot study

    No full text
    Aim: HIV infection and combined antiretroviral therapy (cART) are associated with chronic immune activation, which can contribute to the development of metabolic problems and chronic diseases, e.g., cardiovascular diseases, type-2 diabetes. In the general population moderate physical activity has shown to reduce both inflammation and burden of chronic diseases. Aim of this study was to evaluate the effects of walking, as moderate aerobic exercise, on physical fitness, metabolic measures and soluble and cell inflammatory markers among HIV-infected treated subjects. Methods: A pilot study was designed including HIV-infected, cART-treated, sedentary subjects with metabolic problems, in a 12-week protocol consisting of 3 outdoor sessions/week of 60 min brisk walking at 65-75% of HRmax with (“walk-strength” group) or without (“walk” group) 30 min circuit training at 65% of 1-ripetition maximum (RM). Measures at baseline (BL) and at week 12 (W12) included distance walked at 6 minute walking test (6MWT) and 1-RM Test; morphometric measures; fasting lipid and glucose blood profile; plasma level of d-dimer, high-sensitivity CRP (hsCRP), interleukin-6 (IL-6), interleukin-18 (IL-18), soluble CD14 (sCD14), myostatin, and CD38 and HLA-DR expression on CD4+ and CD8+ cells. Differences between groups were tested by the Mann-Whitney test and W12 changes from BL by the Wilcoxon-signed rank test. Results are expressed as median values. Results: Forty-nine subjects were enrolled and 36 completed the 12-week program: 15 in the "walk-strength" group and 21 in the "walk” group. Median adherence was 67%. At W12, significant improvements from BL were observed of both aerobic and strength performance, with a 14% improvement of distance walked during 6MWT, of BMI, waist and hip circumference, and total and LDL cholesterol, without differences between training groups. Significant reductions were observed of plasma levels of d-dimer (from 272 to 181 ng/mL, p=0.0002), hCRP (from 2.02 to 1.14 μg/mL, p=0.001), IL-6 (from 4.63 to 4.47 pg/mL, p=0.021), IL-18 (from 354 to 304 pg/mL, p=0.010) and myostatin (from 20.9 to 13.5 pg/mL, p=0.006). We observed also a decrease of frequency of CD8+CD38+ HLA-DR (from 3.7 to 1.8%, p<0.0001), but not for CD4+HLA-DR+. Conclusions: A 12-week protocol of brisk walking was associated with a significant reduction of immune activation in HIV- treated subjects with metabolic disorders. Moderate physical activity can be proposed as a strategy to control long-term consequences of treated HIV infection

    The human skeletal muscle glycogenin gene: cDNA, tissue expression, and chromosomal localization

    No full text
    Glycogen synthesis is impaired in first degree relatives of subjects with non-insulin-dependent diabetes mellitus and genes relevant to this metabolic pathway are considered reasonable candidates in the pathogenesis of the disease. In skeletal muscle thede novosynthesis of glycogen is primed by an enzyme named glycogenin. We have cloned the glycogenin cDNA from human skeletal muscle mRNA: human glycogenin is a 333 amino acid protein exhibiting 93% identity with rabbit glycogenin. A single transcript of about 2.4 kb, prominent in skeletal muscle, was detected by Northern blot analysis.In situhybridization unequivocally located the human glycogenin gene to chromosome 3q25.1. Furthermore, we mapped two intronless glycogenin-related sequences to human chromosomes 12 and 13

    Dose Dependent Side Effect of Superparamagnetic Iron Oxide Nanoparticle Labeling on Cell Motility in Two Fetal Stem Cell Populations

    No full text
    Multipotent stem cells (SCs) could substitute damaged cells and also rescue degeneration through the secretion of trophic factors able to activate the endogenous SC compartment. Therefore, fetal SCs, characterized by high proliferation rate and devoid of ethical concern, appear promising candidate, particularly for the treatment of neurodegenerative diseases. Super Paramagnetic Iron Oxide nanoparticles (SPIOn), routinely used for pre-clinical cell imaging and already approved for clinical practice, allow tracking of transplanted SCs and characterization of their fate within the host tissue, when combined with Magnetic Resonance Imaging (MRI). In this work we investigated how SPIOn could influence cell migration after internalization in two fetal SC populations: human amniotic fluid and chorial villi SCs were labeled with SPIOn and their motility was evaluated. We found that SPIOn loading significantly reduced SC movements without increasing production of Reactive Oxygen Species (ROS). Moreover, motility impairment was directly proportional to the amount of loaded SPIOn while a chemoattractant-induced recovery was obtained by increasing serum levels. Interestingly, the migration rate of SPIOn labeled cells was also significantly influenced by a degenerative surrounding. In conclusion, this work highlights how SPIOn labeling affects SC motility in vitro in a dose-dependent manner, shedding the light on an important parameter for the creation of clinical protocols. Establishment of an optimal SPIOn dose that enables both a good visualization of grafted cells by MRI and the physiological migration rate is a main step in order to maximize the effects of SC therapy in both animal models of neurodegeneration and clinical studies

    Adiponectin levels in the serum and cerebrospinal fluid of amyotrophic lateral sclerosis patients : possible influence on neuroinflammation?

    No full text
    BACKGROUND: Adiponectin (APN) is a key player in energy homeostasis strictly associated with cerebrovascular and neurodegenerative diseases. Since APN also belongs to anti-inflammatory-acting adipokines and may influence both neuroinflammation and neurodegenerative processes, we decided to study the APN levels in amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases. METHODS: We assessed APN levels by ELISA immunoassay in both the serum and cerebrospinal fluid of a cohort of familial and sporadic ALS patients, characterized by normal body mass index and absence of dysautonomic symptoms. The screening of serum APN levels was also performed in patients affected by other neurological disorders, including fronto-temporal dementia (FTD) patients. Means were compared using the non-parametric Wilcoxon test, and Pearson's or Spearman's rho was used to assess correlations between variables. RESULTS: In the whole ALS group, serum APN levels were not different when compared to the age- and sex-matched control group (CTR), but a gender-specific analysis enlightened a significant opposite APN trend between ALS males, characterized by lower values (ALS 9.8 ± 5.2 vs. CTR 15 ± 9.7 μg/ml), and ALS females, showing higher amounts (ALS 26.5 ± 11.6 vs. CTR 14.6 ± 5.2 μg/ml). This sex-linked difference was significantly enhanced in familial ALS cases (p ≤ 0.01). The APN levels in ALS cerebrospinal fluids were unrelated to serum values and not linked to sex and/or familiarity of the disease. Finally, the screening of serum APN levels in patients affected by other neurological disorders revealed the highest serum values in FTD patients. CONCLUSIONS: Opposite serum APN levels are gender-related in ALS and altered in several neurological disorders, with the highest values in FTD, which shares with ALS several overlapping and neuropathological features. Further investigations are needed to clarify the possible involvement of APN in neuroinflammation and neurodegeneration. Possible involvement of APN in neuroinflammatory neurodegenerative diseases
    corecore